Liquid transport method

ABSTRACT

A liquid transport method is disclosed for efficiently producing cell cultures. The liquid transport method of the present disclosure, which is in processing of cells, includes: a) a step in which a container holding a liquid is gripped by a gripping tool of a robot; and b) a step in which the liquid in the container is transported to a collection container by rotating the gripped container. In steps a) and b) the robot operates such as not to pass over a vertical line of an opening of the collection container.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/632,937, filed on Jun. 26, 2017, which is a continuation ofInternational Application No. PCT/JP2015/086158, filed on Dec. 25, 2015,which claims priority to Japanese Patent Application No. 2014-265891,filed on Dec. 26, 2014, the entire content of all three of which isincorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to a liquid transport method, a cellprocessing system, and a cell processing method.

BACKGROUND DISCUSSION

In recent years, various attempts to transplant cells have been made forrepair of injured tissues and the like. For example, for repair ofmyocardial tissues injured due to ischemic heart diseases such as anginapectoris and myocardial infarction, utilization of fetal myocardialcells, skeletal myoblasts, mesenchymal stem cells, cardiac stem cells,embryo-stem (ES) cells, etc. has been attempted (See Haraguchi et al.,Stem Cells Transl Med. 2012 February; 1(2): 136-41).

In connection with such attempts, cell structures formed utilizing ascaffold and sheet-shaped cell cultures obtained by forming cells into asheet-shaped form have been developed (See JP2007528755(A), PCT PatentPublication No. WO2006/080434, JP2005229869(A), JP201081829(A),JP2010226991(A), and JP2006149268(A), and Ohashi et al., TransplantProc. 2011 November; 43(9): 3188-91).

In regard of application of sheet-shaped cell cultures to therapy,investigations have been made as to utilization of cultured skin sheetsfor skin injury due to burn or the like, utilization of cornealepithelium sheet-shaped cell cultures for corneal injury, utilization ofmouth mucosa sheet-shaped cell cultures for endoscopic resection ofesophageal carcinoma, etc.

However, such sheet-shaped cell cultures and cell structures must beproduced in clean environments, and high levels of knowledge and skillare required for the production thereof. For this reason, in the past,these cell cultures have been manually produced in a clean room called acell processing center (CPC) by an operator having expert knowledge.Thus, huge cost and labor have been required for the production of suchcell cultures.

In view of this, an automatic cell culture apparatus for performing theoperations concerning culture of the cells by an articulated robot isdisclosed.

SUMMARY

During various studies conducted in this technical field by the presentinventors, attention was paid to the problem that in the case ofautomatically performing all the operations concerning cell culture by arobot, the configuration of the apparatus is complicated, with theresult that maintainability and system extensibility would be relativelypoor, and efficient use would be virtually impossible. A system isdisclosed in which a combination of robot operations and manualoperations can be performed in an integrated manner, which is capable ofmore rationally contributing to the cell culture technology, rather thana method of performing all the operations by depending on a robot orrobots.

Accordingly, a cell processing system is disclosed which enablesefficient production of cell cultures through a rational combination ofrobot operations and manual operations and has a comparatively simpleconfiguration, and a cell processing method, a liquid transport method,and a gripping tool which are for efficient production of cell cultures.

The aforesaid object, which can be achieved by a rational combination ofrobot operations and manual operations, is achieved by, for example, thefollowing means (1) to (30).

(1) A cell processing system, which is a system for use in processing ofcells by use of a container, the cell processing system includes: a baseprovided with a plurality of processing areas for performing processingby use of the container and a carrying-in/carrying-out area where thingsfor use in the processing can be carried in and carried out; a robotthat is provided on the base and has a gripping tool capable of grippingat least part of the container; a housing that covers the processingareas, the robot, and at least part of the carrying-in/carrying-out areaand is able to maintain cleanliness of inside thereof; and at least oneworking section that is disposed on the housing or the base and isconfigured in such a manner that manual operation in the housing fromoutside of the housing can be performed thereby, wherein the grippingtool of the robot can reach the processing areas, the housing isconfigured such that its part adjacent to the carrying-in/carrying-outarea can be opened and closed, and the working section is configuredsuch that its workable area overlaps with the processing area and/or thecarrying-in/carrying-out area, and things for use in the processing canbe moved between the respective processing areas and thecarrying-in/carrying-out area through the working section.

(2) The cell processing system as described in (1), includes a pluralityof the working sections, wherein workable areas of the working sectionsadjacent to each other overlap with each other.

(3) The cell processing system as described in (1) or (2), whereinmanual preparation for the processing in the processing area can beperformed by the working section.

(4) The cell processing system as described in any one of (1) to (3),wherein the processing is performed by the robot.

(5) The cell processing system as described in any one of (1) to (4),wherein the working section is a glove.

(6) The cell processing system as described in any one of (1) to (5),wherein at least one of the processing area is an area for dispensing aliquid into the container.

(7) The cell processing system as described in any one of (1) to (6),wherein at least one of the processing areas is an area for disposing ofthe liquid in the container.

(8) The cell processing system as described in (6) or (7), wherein theliquid is a culture medium.

(9) The cell processing system as described in any one of (1) to (8),wherein the container includes a container main body and a cap, and atleast one of the processing areas is an area for attachment anddetachment of the cap to and from the container main body.

(10) The cell processing system as described in any one of (1) to (9),wherein the system uses for exchange of a culture medium in thecontainer, dispensing of the culture medium into the container,inoculation of cells into the container, and/or dissection of a celltissue formed on an inner wall surface of the container.

(11) A cell processing system, which is a system for use in processingof cells by use of a container, the cell processing system includes: abase provided with at least one processing area for performing theprocessing by use of the container and a containercarrying-in/carrying-out area; a robot that is provided on the base andhas a gripping tool capable of gripping at least part of the container;and a housing that covers at least the processing areas and the robotand is able to maintain cleanliness of inside thereof, wherein thegripping tool of the robot can reach the processing areas, the grippingtool includes a first gripping section, and a second gripping sectionthat is disposed on a distal tip side relative to the first grippingsection and is larger than the first gripping section in separateddistance between gripping surfaces, and the second gripping section hasa configuration in which part thereof is omitted in a vicinity of acenter axis of the first gripping section.

(12) A gripping tool for a robot that is used in operating a containerfor processing cells, the gripping tool includes: a first grippingsection; and a second gripping section that is disposed on a distal tipside relative to the first gripping section and is larger than the firstgripping section in separated distance between gripping surfaces,wherein the second gripping section has a configuration in which partthereof is omitted in a vicinity of a center axis of the first grippingsection.

(13) The gripping tool as described in (12), wherein the second grippingsection is disposed at a position corresponding to an end portion on alateral side of the gripping surface of the first gripping section.

(14) The gripping tool as described in (12) or (13), wherein the secondgripping section is disposed at a position corresponding to both endportions on lateral sides of the gripping surfaces of the first grippingsection.

(15) The gripping tool as described in any one of (12) to (14), whereinthe first gripping section has a recessed part in a vicinity of a centerof the gripping surface, along an axial direction.

(16) The gripping tool as described in any one of (12) to (15), whereinanti-slipping portions are disposed on the gripping surfaces of thefirst gripping section and/or the second gripping section.

(17) A cell processing method for processing cells by use of a pluralityof containers each having a cap and a container main body, the cellprocessing method includes:

1) a step of disposing n (where n is an integer of not less than 2)containers to be processed in a predetermined order;

2) a step of detaching the cap from the container main body of thecontainer to be processed i-thly (where i is an integer satisfying2≤i≤n) and attaching the cap to the container main body of the containerprocessed (i−1) thly, by a robot; and

3) a step of performing the processing by use of the container to beprocessed i-thly.

(18) The cell processing method as described in (17), wherein step 2)and step 3) are repeated until i increases from 2 to n.

(19) The cell processing method as described in (17) or (18), whereinthe robot operates in such a manner as not to pass over an opening ofthe container main body from which the cap has been detached.

(20) The cell processing method as described in any one of (17) to (19),includes, prior to step 2), a step of detaching the cap of the containerto be processed i-thly from the container main body by the robot anddisposing the cap on a cap depository.

(21) The cell processing method as described in any one of (17) to (20),wherein after the processing of step 3) is conducted for the containerto be processed n-thly, the cap disposed on the cap depository isattached to the container main body of the container by the robot.

(22) The cell processing method as described in any one of (17) to (21),wherein the processing in step 3) is disposal of a liquid from thecontainer and/or pouring of a liquid into the container.

(23) The cell processing method as described in (22), wherein the liquidis a culture medium.

(24) The cell processing method as described in any one of (17) to (23),wherein the processing is exchange of a culture medium in the container,dispensing of a culture medium into the container, inoculation of cellsinto the container, or dissection of a cell tissue formed on an innerwall surface of the container.

(25) A liquid transport method in processing of cells, the liquidtransport method includes:

a) a step in which a container holding a liquid is gripped by a grippingtool of a robot; and

b) a step in which the liquid in the container is transported to acollection container by rotating the gripped container,

wherein in steps a) and b), the robot operates in such a manner as notto pass over a vertical line of an opening of the collection container.

(26) The liquid transport method as described in (25), wherein thegripping tool is rotatable, and in step b), the container is rotated, inthe same direction, about a center axis consisting of an axis parallelto an axis of rotation of the gripping tool.

(27) The liquid transport method as described in (25) or (26), whereinin step b), the container is reciprocated up and down when the openingof the container is oriented downward.

(28) The liquid transport method as described in any one of (25) to(27), wherein in step b), the rotation of the container is performedwhile being accompanied by a translational motion.

(29) The liquid transport method as described in any one of (25) to(28), wherein in step a), the gripping of the container is conducted insuch a manner that the gripping tool is not present over a vertical lineof an opening of the container.

(30) The liquid transport method as described in any one of (25) to(29), wherein the liquid is a culture medium.

In accordance with an aspect, a liquid transport method in processing ofcells is disclosed, the liquid transport method comprising: a) a step inwhich lateral sides of a container holding a liquid is gripped by agripping tool of a robot from a cassette configured to hold a pluralityof containers, the cassette having a plurality of recessed parts eachshaped corresponding to a bottom surface of the container, the grippingof the container being conducted in such a manner that the gripping toolis not present over a vertical line of an opening of the container; b) astep in which the liquid in the container is transported into acollection container by rotating the gripped container and orienting theopening of the gripped container toward a vertically lower direction;and wherein in steps a) and b), the robot operates in such a manner asnot to pass over a vertical line of an opening of the collectioncontainer.

In accordance with another aspect, a cell processing system isdisclosed, which is a system for use in processing of cells by use of acontainer, the cell processing system comprising: a base provided with aplurality of processing areas for performing processing by use of thecontainer and a carrying-in/carrying-out area where things for use inthe processing can be carried in and carried out; a robot that isprovided on the base and has a gripping tool capable of gripping atleast part of the container, the robot being adjacent to each of theplurality of processing areas; a housing that covers the processingareas, the robot, and at least part of the carrying-in/carrying-out areaand is able to maintain cleanliness of an inside of the housing; atleast one working section that is disposed on the housing or the baseand is configured in such a manner that manual operation in the housingfrom outside of the housing can be performed thereby; wherein thegripping tool of the robot can reach each of the processing areas; thehousing is configured such that a part of the housing adjacent to thecarrying-in/carrying-out area can be opened and closed; the workingsection is configured such that its workable area overlaps with theprocessing area and/or the carrying-in/carrying-out area, and things foruse in the processing can be moved between the respective processingareas and the carrying-in/carrying-out area through the working section;at least one openable and closeable slide shutter, the at least oneopenable and closeable shutter configured to produce a closed systemwhen the at least one shutter is closed; and a plurality of suctionportions in the base and in a vicinity of the at least one shutter, theplurality of suction portions configured to generate a clean spacehaving a reduced-pressure state in the clean space.

According to the present disclosure, a cell processing system isdisclosed, which enables efficient production of cell cultures and whichhas a comparatively simple configuration, and a cell processing method,a liquid transport method, and a gripping tool which are for efficientproduction of cell cultures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a cell processing system according to afirst embodiment of the present disclosure.

FIG. 2 is a plan sectional view of the cell processing system shownalong lines X-X in FIG. 1.

FIG. 3 is a perspective view of a robot provided in the cell processingsystem shown in FIG. 1.

FIG. 4 is a partial enlarged view of a gripping tool of the robotprovided in the cell processing system shown in FIG. 1.

FIGS. 5(a)-5(c) show schematic views for illustrating an operation ofthe gripping tool shown in FIG. 4.

FIGS. 6(a)-6(c) show schematic views for illustrating an operation ofthe gripping tool shown in FIG. 4.

FIG. 7 is a schematic view showing an example of a container for use inthe cell processing system according to the first embodiment.

FIG. 8 is a schematic view showing an example of a cassette for thecontainers for use in the cell processing system according to the firstembodiment.

FIG. 9 is a flow chart for explaining a cell processing method accordingto the first embodiment of the present disclosure.

FIG. 10 is a flow chart for explaining the cell processing methodaccording to the first embodiment of the present disclosure.

FIGS. 11(a)-11(c) show schematic views for illustrating the cellprocessing method according to the first embodiment of the presentdisclosure.

FIGS. 12(a)-12(g) show schematic views for illustrating a liquidtransport method according to the first embodiment of the presentdisclosure.

FIGS. 13(a)-13(e) show schematic views for illustrating a conventionalliquid transport method.

FIG. 14 is a schematic view for illustrating the cell processing methodaccording to the first embodiment of the present disclosure.

FIG. 15 is a sectional view of a cell processing system according to asecond embodiment of the present disclosure.

FIG. 16 is a sectional view of a cell processing system according to athird embodiment of the present disclosure.

FIG. 17 is a schematic view showing an example of a cassette forcontainers for use in the cell processing system shown in FIG. 16.

FIG. 18 is a schematic view showing another modification of the presentdisclosure.

FIG. 19 is a schematic view showing a further modification of thepresent disclosure.

DETAILED DESCRIPTION

Preferred embodiments of the present disclosure will be described indetail below, referring to the drawings.

Note that in each of the figures in the present application, the sizesof respective members are appropriately exaggerated, for easyexplanation, and the respective members shown in the figures are notshown in the actual sizes.

First, a first embodiment of the present disclosure will be described.

A cell processing system 1 illustrated in FIG. 1 is used for processing(treatment) of cells using a container 100, and used particularly fordischarging a liquid L from the container 100 and pouring (dispensing)the liquid L into the container 100, in culturing cells by use of thecontainer 100 to obtain a cell culture. In the present embodiment, theliquid L is a culture medium, and the cell processing system 1 is aculture medium exchange system used for exchange of the culture medium(liquid L) in the container 100.

In addition, cells to be used in the processing in the cell processingsystem 1 are not particularly limited, and examples of the cells includecells harvested from a subject, and cryopreserved cells.

More specifically, the cells which can be used in the cell processingsystem 1 are not particularly limited, and examples of the cells includeadherent cells (adhesive cells). Examples of the adherent cells includeadherent somatic cells (for example, myocardial cells, fibroblasts,epithelial cells, endothelial cells, hepatic cells, pancreatic cells,renal cells, adrenal cells, periodontal ligament cells, gingival cells,periosteal cells, skin cells, synovial cells, cartilage cells, etc.) andstem cells (for example, myoblasts, cardiac stem cells and the liketissue stem cells, embryonic stem cells, induced pluripotent stem (iPS)cells and the like pluripotent stem cells, mesenchymal stem cells,etc.). The somatic cells may be those differentiated from stem cells,particularly iPS cells. Examples of such cells include myoblasts (forexample, skeletal myoblasts), mesenchymal stem cells (for example, thosederived from bone marrow, adipose tissue, peripheral blood, skin, hairroot, muscular tissue, uterine mucosa, placenta, or umbilical cordblood), myocardial cells, fibroblasts, cardiac stem cells, embryonicstem cells, iPS cells, synovial cells, cartilage cells, epithelial cells(for example, mouse mucosa epithelial cells, retinal pigment epithelialcells, nasal epithelial cells, etc.), endothelial cells (for example,vascular endothelial cells), hepatic cells (for example, hepaticparenchymal cells), pancreatic cells (for example, islet cells), renalcells, adrenal cells, periodontal ligament cells, gingival cells,periosteal cells, skin cells, etc.

In addition, by cell culture including the processing conductedutilizing the cell processing system 1, a cell culture wherein cells areinterlocked each other such as, for example, a sheet-shaped cell culturecan be obtained.

Herein the “sheet-shaped cell culture” refers to a sheet-shaped bodywherein cells are interlocked each other. The cells in the sheet-shapedcell culture may be interlocked each other directly (inclusive of thecase of interconnection through cell elements such as adhesionmolecules) and/or through an intervening substance. In accordance withan exemplary embodiment, the intervening substance is not particularlylimited so long as it is a substance capable of at least physically(mechanically) interlock the cells, and examples thereof include anextracellular matrix. The intervening substance is preferably onederived from cells, for example, particularly one that is derived fromthe cells constituting the sheet-shaped cell culture. The cells areinterlocked at least physically (mechanically), and may be furtherinterlocked functionally, for example, chemically or electrically. Thesheet-shaped cell culture may be one that is composed of one cell layer(monolayer), or may be one that is composed of two or more cell layers(laminated (multilayer), for example, two layers, three layers, fourlayers, five layers, or six layers).

In accordance with an exemplary embodiment, the sheet-shaped cellculture preferably does not include a scaffold (support). A scaffold maybe used in the technical field by adhering cells onto its surface and/orto its inside for the purpose of maintaining the physical integrity ofthe sheet-shaped cell culture, and known examples of the scaffoldinclude a membrane made of polyvinylidene difluoride (PVDF). Inaddition, preferably, the sheet-shaped cell culture is composed of asubstance or substances derived from the cells constituting thesheet-shaped cell culture and does not include other substances.

In accordance with an exemplary embodiment, the aforementioned cells canbe derived from any organism that can be treated by the sheet-shapedcell culture. Such an organism is not limited examples, and examples ofthe organisms can include humans, nonhuman primates, dogs, cats, pigs,horses, goats, sheep, rodent animals (for example, mice, rats, hamsters,guinea pigs), and rabbits.

The cells to be used for forming the sheet-shaped cell culture may beone kind of cells, or may be two kinds of cells. In the case where thecells for forming the sheet-shaped cell culture are two or more kinds ofcells, the proportion (purity) of the most abundant kind of cells is,for example, not less than approximately 60%, preferably not less thanapproximately 70%, and more preferably not less than approximately 75%,at the start of culture for forming a sheet-shaped body or at the end ofproduction of the sheet-shaped cell culture.

In addition, in the present embodiment, as shown in FIGS. 7 and 8, thecontainer 100 is a cell culture flask, and includes a container mainbody 110 having an opening 111, and a cap 120 configured to be capableof screw engagement with the opening 111 of the container main body 110and capable of thereby closing the opening 111. The container main body110 has two main surfaces 112 and 113 as side surfaces thereof, and canbe used for culture of cells with either of the main surfaces 112 and113 as a lower surface.

Note that in the present embodiment the cell processing system 1 is foroperating a plurality of containers 100, and in management and operationof the plurality of containers 100, a cassette 200 as depicted in FIG. 8can be used. The cassette 200 can be a plate-shaped base provided with aplurality of recessed parts 201 on a main surface thereof. Each of therecessed parts 201 is shaped correspondingly to the shape of thecontainer main body 110 such that the container 100 can be disposed inthe recessed part 201 with the cap 120 oriented upward. In addition, therecessed parts 201 can be provided in a row such that the plurality ofcontainers 100 can be aligned in such a manner that the main surfaces112 of the containers 100 are parallel to one another. In addition, thecassette 200 is provided, in a main surface on the side opposite to themain surface formed with the recessed parts 201, with securing holes(not shown) in which securing pins 127 to be described later can beengaged.

The cell processing system 1 illustrated in FIGS. 1 and 2 includes abase 10, a robot 20, a housing 30, and working sections 40.

The base 10 is a working table on which to perform processing of cellsin the cell processing system 1. As shown in FIG. 2, the base 10 isrectangular in plan-view shape. On the base 10, acarrying-in/carrying-out area 11 is disposed in the vicinity of one end,and a plurality of processing areas 12A to 12C are disposed in otherareas than the carrying-in/carrying-out area 11. In addition, the base10 is provided with an operation section 13 at a side surface in thevicinity of the carrying-in/carrying-out area 11.

The carrying-in/carrying-out area 11 is an area used for carrying-in andcarrying-out of the containers 100, the cassette 200, materialsnecessary for processing of cells, and things for use in processing suchas chemicals, culture medium, instruments, and devices. In the presentembodiment, the carrying-in/carrying-out area 11 is entirely disposedunder a space (clean space) 15 formed by the housing 30 which isdescribed later. In accordance with an exemplary embodiment, an operatorpresent in the external environment can dispose things to be used in theprocessing on the carrying-in/carrying-out area 11 through a shutter 32of the housing 30 which will be described later. In addition, ifnecessary, the operator can perform appropriate operations over thecarrying-in/carrying-out area 11.

In accordance with an exemplary embodiment, the processing areas 12A to12C are disposed adjacently to the robot 20 and the working sections 40which will be described later. The processing areas 12A to 12C are areasin which processing is performed. In the processing areas 12A and 12C,things for use in the processing is disposed in accordance with thecontents of the processing.

Specifically, the processing area 12A is a dispensing area in which todispense a liquid into the container 100. Therefore, a dispensing pump121, a culture medium storage container 122 for storing a culturemedium, a tube 123 for supplying the culture medium from the culturemedium storage container 122 into the container 100 by the dispensingpump 121, and a liquid measurement sensor 124 for measuring the amountof the liquid dispensed into the container 100 are disposed in theprocessing area 12A.

The processing area 12B is a culture medium collection area fordisposing of and collecting the culture medium in the container 100. Acollection container 125 for collecting the culture medium transportedfrom the container 100 and a sensor 126 for measuring the collectionamount are disposed in the processing area 12B. In accordance with anexemplary embodiment, the collection container 125 is a bottle having acomparatively large capacity, and the sensor 126 is a weight sensordisposed under the collection container 125. Note that the sensor is notlimited to this one, and may be, for example, an optical sensor thatoptically detects the amount of liquid.

In accordance with an exemplary embodiment, the processing area 12C is acap attachment/detachment area for attaching and detaching the cap 120of the container 100. Securing pins 127 as securing means for securingthe cassette 200 for the containers 100 and a cap depository 128 forsupporting the cap 120 detached from the container 100 are disposed inthe processing area 12C. The securing pins 127 have shapes correspondingto the securing holes in the cassette 200, and can secure the cassette200 through engagement with the securing holes. The cap depository 128is shaped correspondingly to the cap 120, and is configured to becapable of screw engagement with the cap 120.

The operation section 13 shown in FIG. 1 is configured such as toperform at least part of operations for controlling the robot 20 in thecell processing system 1, respective instruments in the processing areas12A to 12C, and the atmosphere (environment) in the space 15 which willbe described later, and includes various input sections 131 and adisplay section 132.

The input sections 131 are configured in such a manner that commands tothe cell processing system 1 can be inputted by the operator. Thecommands inputted at the input sections 131 are transmitted to a controlsection (not shown) in the base 10, and control of the cell processingsystem 1, specifically, control of the robot 20 and the atmosphere isperformed by the control section. Note that while the input sections 131are composed of pluralities of buttons and handles in the presentembodiment, these are not restrictive. For example, in accordance withan exemplary embodiment, the input sections 131 can be configured by useof pointing devices such as a mouse, a trackball, and a pen tablet,connection terminals such as a keyboard, a touch panel, or input,output, or input/output terminals, a joystick, or a three-dimensionaltactile-sense/force-sense interface device, either singly or incombination.

The display section 132 is a display for displaying informationconcerning the cell processing system 1, such as the state of the cellprocessing system 1 and the contents of inputted commands. The displaysection 132 is configured to be capable of communication with thecontrol section, and can display information in response to the commandsfrom the control section. Note that while the display section 132 is adisplay in the present embodiment, this is not restrictive. For example,the display section 132 may be lamps, a touch panel or the like, or maybe configured by a combination of these.

In addition, the base 10 is provided with suction ports 14 in thevicinity of the shutter 32 to be described later, in thecarrying-in/carrying-out area 11. Air in the clean space 15 is suckedthrough the suction ports 14 to establish a reduced-pressure state inthe clean space 15, whereby unintentional leakage to the exterior of thecell processing system 1 can be prevented from occurring. In addition,an airflow generated between the suction ports 14 and an air supply portwhich will be described later form an air curtain in the vicinity of theshutter 32, whereby foreign matter can be prevented from mixing into theclean space 15 from the exterior of the cell processing system 1. Inaccordance with an exemplary embodiment, the air sucked through thesuction ports 14 is appropriately sterilized by sterilizing means (notshown) such as a high efficiency particular air (HEPA) filter disposedin the cell processing system 1, and discharged to the exterior of thecell processing system 1.

As illustrated in FIG. 3, the robot 20 is a vertical articulated robotdisposed in the vicinity of the center of the base 10. In accordancewith an exemplary embodiment, the robot 20 has six axes. The robot 20can include a base 21 which can be turned relative to the base 10, afirst arm 22 which is interlocked to the base 21 and can be tiltedrelative to a vertical axis about which the base 21 is turned, a secondarm proximal section 23 which is interlocked to a distal side of thefirst arm 22 and can be tilted relative to the first arm 22, a secondarm distal section 24 which is interlocked to a distal side of thesecond arm proximal section 23 and can be rotated relative to an axialdirection of the second arm proximal section 23, a hand section 25 whichis interlocked to a distal side of the second arm distal section 24 andcan be tilted relative to an axial direction of the second arm distalsection 24, and a gripping tool (gripper) 26 interlocked to the handsection 25. In accordance with an exemplary embodiment, the hand section25 is configured to be rotatable about an axial direction thereof.

In addition, the robot 20 is configured such that its gripping tool 26can reach an area indicated by an alternate long and short dash line inFIG. 2 and, therefore, can reach a desired position in each of theprocessing areas 12A to 12C in a desired posture. As a result,operations in the processing areas 12A to 12C by the robot 20 can beperformed.

In addition, the robot 20 is connected to a controller 300 and a controlterminal 400 disposed in the exterior of the cell processing system 1shown in FIG. 1, and can automatically perform operations according tothe commands inputted from the control terminal 400.

Configured in this manner, the robot 20 can perform determination of theposition and posture of the gripping tool 26 as well as rotation andopening/closing operations of the gripping tool 26, whereby thecontainer 100 can be gripped and operated by the gripping tool 26. Morespecifically, for example, by gripping the container 100 by the grippingtool 26, the container 100 can be transported, tilted, and rotated, and,by gripping the cap 120 and rotating the gripping tool 26, the cap 120can be detached from the container main body 110 or attached to thecontainer main body 110.

Now, the gripping tool 26 will be described more in detail.

The gripping tool 26 depicted in FIG. 4 is a parallel gripper, and caninclude a gripping tool main body 261 interlocked to the hand section 25on the proximal side thereof, a pair of guide members 262 disposed onthe distal side of the gripping tool main body 261 and slidable, and apair of claw sections (fingers) 263 secured to the guide members 262.

The gripping tool main body 261 is provided therein with an actuator anda linear guide (both not shown), and operates the guide members 262 bybeing externally supplied with a command and power such as electricpower. The guide members 262 are secured in the direction of sliding bythe linear guide, and the guide members 262 can be accurately broughtcloser to or away from each other.

In accordance with an exemplary embodiment, the pair of claw sections263 are secured individually to the pair of guide members 262, and canbe brought closer to or away from each other according to the operationof the guide members 262. As a result, the claw sections 263 can grip atleast part of the container 100.

The claw section 263 includes a first gripping section 264 provided on aproximal side, and a second gripping section 265 provided on the distalside (distal tip side) with reference to the first gripping section 264.In addition, the second gripping section 265 is configured such that theseparated distance between its gripping surfaces 267 is greater than theseparated distance between gripping surfaces 266 of the first grippingsection 264. Since the claw sections 263 have two sets of grippingsections differing in separated distance, namely, in gripping width, thesize of the gripping tool 26 can be reduced by reducing a stroke of thegripping tool 26, and bodies (works) with different sizes can begripped. As a result, as shown in FIGS. 6(a) to 6(c), the cap 120 of thecontainer 100 can be gripped by the first gripping section 264, and, onthe other hand, as shown in FIGS. 5(a) to 5(c), the container main body110 of the container 100 can be gripped by the second gripping section265. In addition, by rotating the first gripping section 264 togetherwith the claw sections 263 while gripping the cap 120, the cap 120 canbe detached from the container main body 110 and to attach the cap 120to the container main body 110.

In addition, anti-slipping portions are disposed on the grippingsurfaces 266 of the first gripping section 264. This helps ensure thatthe cap 120 can be held by the first gripping section 264 more securely,and, in the case of rotating the cap 120 by the first gripping section264, a rotating force can be transmitted from the first gripping section264 to the cap 120 more reliably. In addition, as a result, for example,the gripping force by the first gripping section 264 can be setcomparatively weak, whereby the work as an object to be gripped, such asthe cap 120, is prevented from being damaged. The method for configuringthe anti-slipping portions is not particularly limited, and examples ofthe method include a method wherein a high-frictional-coefficientmaterial such as rubber or elastomer is disposed on the grippingsurfaces, and a method wherein the gripping surfaces 266 are knurled andthereby enhanced in friction.

In addition, as shown in FIG. 4, the second gripping section 265 has aconfiguration wherein part thereof is omitted in the vicinity of acenter axis I of the first gripping section 264. This ensures that whenthe cap 120 is gripped by the first gripping section 264 and the cap 120together with the first gripping section 264 is rotated with the centeraxis I as an axis of rotation, the second gripping section 265 can beprevented from interfering with the container main body 110 of thecontainer 100.

Note that herein the center axis I is a center axis as viewed from thepair of gripping surfaces 266, specifically a center axis which isparallel to the main surfaces of the pair of gripping surfaces 266 ofthe first gripping sections 264 and is directed from the proximal sidetoward the distal side of the first gripping section 264.

More specifically, in the present embodiment, the second grippingsection 265 is disposed at a position corresponding to both end portionson lateral sides of the gripping surfaces 266 of the first grippingsection 264. Specifically, for example, the second gripping section 265is composed of four claws projecting toward the distal side from bothend portions on lateral sides of the first gripping section 264, and isconfigured such as to grip two points individually by two claws. By sucha configuration, as shown in FIG. 6(c), the second gripping section 265can be more securely prevented from interfering with the container mainbody 110. In addition, as depicted in FIG. 5(c), the second grippingsection 265 can grip and fix the container main body 110 at a pluralityof positions, which helps ensure that when the container main body 110is gripped by the second gripping section 265, the container main body110 is prevented from being rotated and tilted unintentionally. Inaddition, since the position of the second gripping section 265 is atboth ends, in the presence of a rotation moment generated about one side(for example, the lower side) of the second gripping section 265, theother side of the second gripping section 265 can sufficiently supportthe container main body 110.

In accordance with an exemplary embodiment, anti-slipping portions aredisposed on the gripping surfaces 267 of the second gripping section265. As a result, the container 100 can be gripped relatively moresecurely by the second gripping section 265. In addition, a work such asthe container 100 can be sufficiently gripped even with a comparativelyweak gripping force, so that the work such as the container 100 can beprevented from being broken.

The housing 30 shown in FIGS. 1 and 2 is configured such as to cover thecarrying-in/carrying-out area 11, the processing areas 12A and 12C, andthe robot 20 on the base 10 and to shield the space 15 over the base 10from the atmosphere in the outside of the cell processing system 1. Thehousing 30 includes side walls 31 and the shutter 32 erected in thevicinity of peripheral portions of the base 10, and a ceiling section 33which seals from above the space 15 defined by the side walls 31 and theshutter 21.

In accordance with an exemplary embodiment, a fan-filter unit (notshown) composed by combining a filter such as a HEPA filter with a fancan be incorporated in the ceiling section 33. Air is sucked from theexterior of the cell processing system 1, and is sterilized and deprivedof foreign matter, and clean air is supplied through an air supply port(not shown) onto the space 15. With clean air thus supplied to the upperside of the base 10 while shielding from the atmosphere in the outsideof the cell processing system 1, the space 15 over the base 10 becomes aclean space 15 where a clean atmosphere is maintained.

In accordance with an exemplary embodiment, the cell processing system 1is configured in such a manner that the cleanliness in the clean space15, for example, is International Organization for Standardization (ISO)class 1 to 9, preferably ISO class 1 to 8, more preferably ISO class 1to 7, in accordance with ISO 14644-1.

In addition, the shutter 32 is a part provided adjacently to thecarrying-in/carrying-out area 11, and is a slide shutter configured tobe openable and closable. When the shutter 32 is closed, the clean space15 is a closed system, and the clean atmosphere therein is maintainedmore securely. On the other hand, when the shutter 32 is opened, thingsfor use in processing can be moved between the cell processing system 1and the external environment through the carrying-in/carrying-out area11, and, in addition, the operator present in the external environmentcan perform operations in the carrying-in/carrying-out area 11. Inaddition, in accordance with an exemplary embodiment, the size of theopening defined by the shutter 32 can be appropriately controlled.

In accordance with an exemplary embodiment, the side walls 31 and theshutter 32 constituting the housing 30 are both formed of a transparentmaterial, for example, resin, so that the inside of the housing 30 canbe observed therethrough.

The working sections 40A to 40D are instruments or tools which aredisposed along the side walls 31 of the housing 30 and configured suchthat manual operations (workings) within the housing 30, namely, forexample, in the clean space 15 from the exterior of the housing 30 canbe performed. In the present embodiment, the working sections 40A to 40Dare pairs of gloves disposed such as to penetrate the side wall 31,which helps permit the operator present in the exterior of the cellprocessing system 1 to perform transport of things necessary forprocessing of cells using the container 100 and preparation for theprocessing, in the clean space 15 by use of the working sections 40A to40D.

In addition, the areas in which the working sections 40A to 40D can beoperated, namely, working areas 41A to 41D, indicated by broken lines inFIG. 2 are overlapping with some of the processing areas 12A to 12Cand/or the carrying-in/carrying-out area 11. Specifically, the workingsection 40A has its working area 41A overlapping with thecarrying-in/carrying-out area 11 and the processing areas 12A and 12B.The working section 40B has its working area 41B overlapping with theprocessing area 12B. The working section 40C has its working area 41Coverlapping with the carrying-in/carrying-out area 11 and the processingarea 12C. The working section 40D has its working area 41D overlappingwith the processing area 12C.

Further, although the working areas 41B and 41D of the working sections40B and 40D do not overlap with the carrying-in/carrying-out area 11,they on the other hand overlap with the working areas 41A and 41C of theworking sections 40A and 40C to which they are adjacent, respectively,which helps ensure that although the working sections 40B and 40D havetheir working areas 41B and 41D not overlapping with thecarrying-in/carrying-out area 11, they are configured such that thethings for use in the processing can be moved through the working areas41A and 41C of the working sections 40A and 40C with which they overlap.

According to the working sections 40A to 40D configured as above, manualpreparation for processing, namely, carrying-in and carrying-out ofthings for use in the processing, disposition of the things, can beperformed in each of the processing areas 12A to 12C. The preparationfor each processing is generally complicated, but, by manuallyperforming such operations, the device configuration of the cellprocessing system 1 can be made to be comparatively simple. In addition,for example, confirmation of the amount of a culture medium necessaryfor exchange, confirmation of disposed states of respective instrumentsfor use in processing, etc. are more readily carried out by manualoperation by the operator than by introduction of devices provided withsensors or the like. On the other hand, in regard of comparativelysimple processing which need to be carried out repeatedly, such asattachment and detachment of the cap 120, or disposal and dispensing ofthe liquid (culture medium), the operations can be carried outrelatively speedily and accurately by the robot 20.

In the cell processing system 1, comparatively simple operations whichneed to be performed repeatedly are automatically carried out by thecell processing system 1 including the robot 20, and the otheroperations are carried out by the operator. Where the operations to beperformed are thus divided among the operator and the robot 20 inaccordance with the kinds of the operations, the operations inclusive ofthe processing conducted in the cell processing system 1 can be carriedout relatively more efficiently, and the device configuration of thecell processing system 1 can be made to be comparatively simple.

In accordance with an exemplary embodiment, the gripping tool 26 caninclude the first gripping section 264 and the second gripping section265 which are different in separated distance as above-mentioned, andpart of the second gripping section 265 is omitted in the vicinity ofthe center axis I of the first gripping section 264. According to thisconfiguration, differently sized works such as the container main body110 and the cap 120 can be gripped by the same gripping tool 26. Inaddition, even in the case where the cap 120 is rotated by the firstgripping section 264, interference between the second gripping section265 and the container main body 110 can be prevented from occurring. Asa result, a situation wherein a plurality of robots are disposed fordifferently sized works or wherein the gripping tool is enlarged inmechanism for enlarging the stroke of the gripping tool, with the resultof enlargement of the overall size of the robot, can be obviated.Accordingly, by adopting such a configuration as that of the grippingtool 26, the configuration of the cell processing system 1 can berelatively simplified.

Now, a cell processing method and a liquid transport method of thepresent embodiment using the aforementioned cell processing system 1will be described below.

In accordance with an exemplary embodiment, since the cell processingsystem 1 is one for use in exchange of a culture medium, the liquid tobe exchanged is a culture medium in the present embodiment. In addition,description will be made based on a situation in which in the container100 to be used, a sheet-shaped cell culture (cell tissue) 114 culturedby a culture medium L is supported on (adhered to) an inner wall surfaceof a main surface 113.

In addition, the cell processing method of the present embodimentincludes, in regard of processing of cells:

1) a step of disposing n (where n is an integer of not less than 2)containers which are to be processed in a predetermined order;

2) a step of detaching a cap of a container to be processed i-thly(where i is an integer satisfying 2≤i≤n) from a container main body andattaching the cap to a container main body of a container processed(i−1)thly, by a robot; and

3) a step of performing processing by use of the container to beprocessed i-thly.

In addition, the liquid transport method of the present embodimentincludes:

a) a step of gripping a container that holds a liquid by a gripping toolof a robot; and

b) a step of transporting the liquid in the container to a collectioncontainer by rotating the gripped container,

wherein in steps a) and b) the robot does not pass over a vertical lineof an opening of the collection container.

First, a power source or sources for the cell processing system 1 and aperipheral system or systems for use therefor (for example, thecontroller 300 and the control terminal 400) are switched ON, to startthe cell processing system 1 (S-1).

Next, instruments and materials for dispensing are disposed and preparedin the processing area 12A which is a dispensing area (S-2). Morespecifically, a substrate and materials are disposed on thecarrying-in/carrying-out area 11, and thereafter the dispensing pump121, the culture medium storage container 122, the tube 123, and theliquid measurement sensor 124 are disposed in thecarrying-in/carrying-out area 11 by the operator either directly or byuse of the working section 40A. In addition, after the disposition,priming is conducted, if necessary.

Subsequently, instruments and materials for collection of a culturemedium are disposed and prepared in the processing area 12B which is aculture medium collection area (S-3). Specifically, the collectioncontainer 125 and the sensor 126 are disposed in thecarrying-in/carrying-out area 11, and thereafter they are transported tothe processing area 12B by the working section 40A. Thereafter, thecollection container 125 and the sensor 126 are disposed by the workingsection 40A or the working section 40B.

Next, preparation for attachment/detachment of a cap is conducted in theprocessing area 12C which is a cap attachment/detachment area (S-4).Specifically, for example, a plurality of containers 100 each containinga culture medium is disposed on the cassette 200, and the cassette 200is temporarily disposed in the carrying-in/carrying-out area 11.Thereafter, the cassette 200 is transported to the processing area 12Cby the working section 40C. The cassette 200 is then secured to theprocessing area 12C by securing the securing pins 127 by the workingsection 40C or the working section 40D.

In accordance with an exemplary embodiment, the respective instrumentsor tools in the processing area 12A as the dispensing area and theprocessing area 12B as the culture medium collection area are alsosecured, if necessary, for example, by securing pins or the like withinranges having predetermined positioning accuracies.

In addition, in the present embodiment, the robot 20 is configured insuch a manner that the order of priority of the containers 100 to beprocessed is determined according to the positions of the recessed parts201 of the cassette 200. Therefore, the order in which to process thecontainers 100 is determined by disposing the containers 100 on thecassette 200. Then, the cassette 200 is secured to the processing area12C, whereby step 1) according to the present embodiment can be carriedout.

Subsequently, commands are inputted by the control terminal 400 tooperate the controller 300 (S-5), and an automatic operation by the cellprocessing system 1 inclusive of the robot 20 is carried out (S-6). As aresult, the cell processing system 1 including the robot 20automatically performs predetermined operations according to thecommands, and exchanges the culture medium in each of the containers100.

Note that the operation (S-6) of the robot 20 is performed along theflow chart shown in FIG. 10.

First, the cap 120 of the container 100 to be processed i-thly(initially, i=1) is detached from the container main body 110.Specifically, the gripping tool 26 is moved onto the container 100 to beprocessed on the cassette 200 by the robot (A-1). Next, the cap 120 isgripped by the first gripping section 264 of the gripping tool 26 (A-2).Subsequently, the cap 120 is rotated a predetermined number of times byrotating the gripping tool 26, to release the screw engagement betweenthe cap 120 and the container main body 110 (A-3). Normally, therotating direction is counterclockwise as the cap 120 is viewed from thegripping tool 26. In addition, the number of times of rotation is set ata number of times sufficient for releasing the screw engagement. Next,the cap 120 released from the screw engagement is lifted upward by thegripping tool 26. By this, the cap 120 is detached from the containermain body 110.

Subsequently, the detached cap 120 is disposed at a predeterminedposition by the gripping tool 26.

In the case where i=1, as shown in FIG. 11(a), the gripping tool 26gripping the cap 120 is moved to an upper side of the cap depository 128(A-4), and is rotated a predetermined number of times in a state whereinthe cap depository 128 and the cap 120 are in contact with each other,to screw-engage the cap depository 128 and the cap 120 (A-5).Thereafter, the gripping of the cap 120 by the gripping tool 26 isreleased.

On the other hand, in accordance with an exemplary embodiment, in thecase where i=2 or above, as illustrated in FIGS. 11(b) and 11(c), thedetached cap 120 is attached to the container main body 110 processed(i−1)thly (step 2)). For example, in the case where i is 2, as shown inFIG. 11(b), the cap 120 of the container 100 to be processed secondly isattached to the container main body 110 processed firstly, and, as shownin FIG. 11(c), the cap 120 of the container 100 to be processed thirdlyis attached to the container main body 110 processed secondly.

By this, an operation of detaching the cap 120 for processing and anoperation of attaching the cap 120 after processing can be carried outsimultaneously. Therefore, a process wherein an operation of temporarilydisposing the cap 120 at the cap depository 128 upon detachment of thecap 120 and thereafter moving the cap 120 from the cap depository 128 toattach the cap 120 onto the container main body 110 is conducted at eachoccasion can be omitted. Therefore, an operation path and an operationtime required for detachment and attachment of the cap 120 can beshortened, and the time for which the inside surface of the cap 120 isexposed to the external environment is shortened, so that contaminationcan be prevented. As a result, overall reliability of the cellprocessing method using the cell processing system 1 can be enhanced.

Specifically, the gripping tool 26 gripping the cap 120 is moved to theupper side of the opening portion of the container main body 110processed (i−1)thly (A-6), and is rotated a predetermined number oftimes in a state in which the opening portion and the cap 120 are incontact with each other to screw-engage the container main body 110 andthe cap 120 with each other (A-7). Thereafter, the gripping of the cap120 by the gripping tool 26 is released.

Next, in regard of the container 100 from which the cap 120 has beendetached, processing is conducted (step 3)). In the present embodiment,the culture medium (liquid) L in the container main body 110 is disposedof, and a fresh culture medium is poured into the container 100, wherebythe culture medium in the container 100 is exchanged.

In regard of the processing, first, the container main body 110 isgripped (step a)). Specifically, the gripping tool 26 is moved to alateral side of the container main body 110 (A-8), and the containermain body 110 is gripped from the lateral side by the second grippingsection 262 of the gripping tool 26 (A-9). In accordance with anexemplary embodiment, the lateral sides of the container main body 110are gripped by the gripping tool 26, whereby the robot 20 inclusive ofthe gripping tool 26 is prevented from passing over the opening of thecontainer main body 110. In addition, also at the time of moving thegripping tool 26 to the lateral side of the container main body 110, itis preferable that the robot 20 inclusive of the gripping tool 26 doesnot pass over the opening of the container main body 110. As a result,dust or the like adhering to the robot 20 can be prevented fromunintentionally dropping into the container main body 110.

Thereafter, the container main body 110 is transported into the vicinityof the collection container 125 in the processing area 12B which is theculture medium collection area (A-10).

Subsequently, the gripped container main body 110 is rotated, wherebythe culture medium L in the container main body 110 is transported intothe collection container 125 (step b) and A-11). In the presentembodiment, as depicted in FIGS. 12(a) to 12(g), the rotation of thecontainer main body 110 is conducted by rotating the container main body110 about a center axis consisting of an axis parallel to the axis ofrotation of the gripping tool 26, in the same direction.

In general, in the case of transporting the culture medium L from thecontainer main body 110 into the collection container 125 by manualoperation, as shown in FIGS. 13(a) to 13(e), upon discharging theculture medium L by once tilting the container main body 110 thecontainer main body 110 is usually turned back (FIG. 13(d)) in adirection opposite to the tilting direction, whereby the opening 111 ofthe container main body 110 is oriented vertically upward. In this case,the culture medium L is liable to remain in the vicinity of a lower sidetoward which the opening 111 of the container main body 110 is tilted,and dripping of the culture medium L from the opening 111 of thecontainer main body 110 to the outside of the opening 111, namely,so-called liquid dripping may occur (FIG. 13(e)). In such a case,contamination of the inside of the container main body 110 starting fromthe culture medium L flowing out due to the liquid dripping tends tooccur.

On the other hand, in the present embodiment, the culture medium Lremaining in the vicinity of the lower side toward which the opening 111is once tilted is located in the vicinity of the upper side of theopening 111, since the container main body 110 is rotated in the samedirection and the opening 111 is thereby reversed downside up (FIGS.12(e) and 12(f)). By this, a situation wherein the culture medium L istransported to an outer peripheral wall surface of the opening 111 tocause liquid dripping can be prevented (FIG. 12(g)).

Note that while the container main body 110 is configured such as to berotated about a center axis consisting of an axis parallel to the axisof rotation of the gripping tool 26 by the robot 20, with such an axisserving as the center axis, 360° rotation of the container main body 110in the same direction by the robot 20 is possible.

In addition, the rotation of the container main body 110 may beperformed while being accompanied by a translational motion. By this,the opening 111 of the container main body 110 can be disposed in thevicinity of the opening of the collection container 125, so that theculture medium L is transported into the collection container 125 moreeasily and reliably.

Further, at the time when the container main body 110 has been rotatedand the opening 111 is oriented toward the vicinity of a verticallylower direction, the container main body 110 is preferably reciprocatedup and down. With such an operation, the culture medium L can betransported from the container main body 110 into the collectioncontainer 125 more reliably.

In addition, the sensor 126 present on a lower side of the collectioncontainer 125 can measure the amount of the culture medium L collected.Therefore, such problems as whether or not the culture medium L has beentransported properly or whether there is abnormality in a cell culturein the container main body 110 can be surmised based on the amount ofthe culture medium L.

Note that in the present embodiment, in the aforesaid processing fordisposing of the culture medium, namely, in steps a) and b), the robot20 is operated in such a manner as not to pass over a vertical line ofthe opening of the collection container 125. By this, foreign matterssuch as dusts and abrasion debris adhering to the robot 20 are preventedfrom mixing into the collection container 125. In analyzing the culturemedium in the collection container 125 including analyzing whether thecell culturing in the container 100 has been performed normally, thepresence of such foreign matter may hamper the analysis. In the presentembodiment, mixing of such foreign matter can be prevented, and wherebythe cell processing system 1 and the cell processing method can beenhanced in reliability.

After the culture medium L is transported from the container main body110 into the collection container 125 as above, a fresh culture medium Lis dispensed into the container main body 110. Specifically, first,while the container main body 110 is kept gripped by the gripping tool26, it is transported to the processing area 12A which is a dispensingarea (A-12). Next, the dispensing pump 121 is operated to dispense apredetermined amount of the fresh culture medium L into the containermain body 110 through the tube 123 (A-13). Note that the dispensingamount is being measured by the liquid measurement sensor 124 with thelapse of time, whereby the final dispensing amount is controlled.

In accordance with an exemplary embodiment, it can be preferable toperform the dispensing in such a manner that the culture medium Lsupplied through the tube 123 does not make direct contact with the cellculture 114 in the container main body 110. For example, in the casewhere the cell culture 114 is cultured on and adhering to a main surface113 on one side of the container main body 110 as shown in FIG. 14, itis preferable to supply the culture medium L from the opening 111 in astate in which the container main body 110 is tilted such that the mainsurface 113 is located on the upper side and a main surface 112 islocated on the lower side. By this, unintentional damage to ordissection of the cell culture 114 can be prevented.

Next, the container main body 110 is transported to the upper side ofthe cassette 200 (A-14), and is thereafter disposed at a lower positionin the recessed part 201 of the cassette 200 (A-15).

The above steps A-1 to A-13 are repeated until i increases from 1 to nwhich is the number of the containers 100, whereby exchange of theculture medium L in each of the containers 100 can be performedautomatically.

In accordance with an exemplary embodiment, as soon as the containermain body 110 with the fresh culture medium L once dispensed thereintois disposed in the recessed part 201, the cap 120 of the container 100to be processed next is attached to the container main body 110 (A-7).

In addition, in the case where there is no container 100 to be processednext, namely, in regard of the container 100 to be processed n-thly, thecap 120 disposed on the cap depository 128 is attached thereto.

Specifically, the gripping tool 26 is moved onto the cap depository 128(A-16), and the cap 120 disposed on the cap depository 128 is gripped bythe second gripping section 264 of the gripping tool 26 (A-17). Next,the cap 120 is rotated by rotating the gripping tool 26, to release thescrew engagement between the cap depository 128 and the cap 120 (A-18).Subsequently, the cap 120 is disposed on the container main body 110,and the gripping tool 26 is rotated together with the cap 120 in a statewhere the cap 120 is in contact with the opening 111 of the containermain body 110, to screw-engage the cap 120 and the container main body110 (A-19).

In accordance with an exemplary embodiment, the aforementioned automaticoperation conducted using the robot 20 is configured such that under apredetermined condition, for example, in the case where the processinghas been finished for all the containers 100 on the cassette 200, in thecase where the culture medium in an amount of not less than apredetermined amount has been transported into the collection container125, in the case where the amount of the culture medium L in the culturemedium storage container 122 has decreased to or below a predeterminedamount, or in the case where other unexpected phenomenon is generated,the automatic operation is stopped, whereas in the case where such acondition is not generated, the automatic operation is continued (S-7).

In this case, the operator, for example, first checks whether or not theprocessing for all the containers 100 on the cassette 200 has beenfinished, and whether or not there is any other container 100 to beprocessed that is not on the cell processing system 1 (S-8).

In the case where a container 100 to be processed is present, it is nextchecked whether or not the culture medium L is present in the culturemedium storage container 122 (S-9), and, if the culture medium L is notpresent, the culture medium L is added to the culture medium storagecontainer 122, or the culture medium storage container 122 is replacedby one filled with a new culture medium L (S-10).

Next, it is checked whether or not a predetermined amount of the culturemedium L is present in the collection container 125 (S-11), and, if thepredetermined amount of the culture medium L is present, the culturemedium L is transferred into other container and disposed of, or thecollection container 125 is replaced by a new collection container 125(S-12).

Subsequently, the cassette 200 is collected, the containers 100 havingundergone the processing are collected, the remaining containers 100 areadded to the cassette 200, and the aforesaid step S-4 is carried out.

In addition, in the case where in step S-7 there is no container 100 tobe processed, the instruments and materials for performing dispensingare detached and removed in the processing area 12A (S-13), disposal ofthe collected culture medium L and removal of instruments and materialsare conducted in the processing area 12B (S-14), and removal of thecassette 200 is conducted in the processing area 12C (S-15).

Thereafter, the power source for the cell processing system 1 is turnedOFF, and the operations are finished (S-16).

Thus, by the method according to the present embodiment, processing ofcells can be performed relatively efficiently.

Particularly, for example, in the culture medium disposal treatment, therobot 20 is configured to operate in such a manner as not to pass overthe vertical line of the opening of the collection container 125,whereby analysis of the collected culture medium L is facilitated, andreliability of the cell processing can be enhanced.

In addition, especially, the operation of detaching the cap 120 forperforming processing and the operation of attaching the cap 120 afterthe processing are conducted simultaneously, whereby the operation pathand operation time required for the detachment and attachment of the cap120 can be shortened, and the time for which the inside surface of thecap 120 is exposed to the exterior environment is shortened, so thatcontamination can be prevented. As a result, total reliability of thecell processing method conducted using the cell processing system 1 canbe enhanced.

A second embodiment of the present disclosure will be described below.

FIG. 15 is a sectional view of a cell processing system according to thesecond embodiment of the present disclosure. Note that in the figure thesame configurations as those in the cell processing system 1 are denotedby the same reference symbols as used above.

Hereinafter, differences between the present embodiment and the firstembodiment will be described in detail, and, in regard of similar items,descriptions thereof will be omitted.

A cell processing system 1A according to the present embodimentillustrated in FIG. 15 differs from the cell processing system 1according to the first embodiment, mainly in that it is a system fordissection of a cell culture cultured in a container 100.

A base 10A in the present embodiment is provided with a processing area12D for dispensing a buffer, in place of and at similar position to theprocessing area 12A which is the culture medium dispensing area, andwith a processing area 12E for dispensing a cell dissociation agent, onthe depth side as viewed from the carrying-in/carrying-out area 11 onthe base 10A.

Dispensing pumps 121A and 121B, storage containers 122A and 122B, tubes123A and 123B, and liquid measurement sensors 124A and 124B are disposedin the processing areas 12D and 12E, respectively. The dispensing pumps121A and 121B, the storage containers 122A and 122B, the tubes 123A and123B, and the liquid measurement sensors 124A and 124B haveconfiguration similar to that of the dispensing pump 121, the culturemedium storage container 122, the tube 123, and the liquid measurementsensor 124 except for differences in the liquid used.

The buffer dispensed in the processing area 12D is not particularlylimited, and examples thereof include acetate buffer, phosphate buffer,citrate buffer, borate buffer, tartrate buffer, TRIS buffer, andphosphate buffered physiological saline solution.

In addition, the cell dissociation agent dispensed in the processingarea 12E is not particularly limited, and examples thereof includecollagenase, trypsin, dispase, ethylenediaminetetraacetic acid (EDTA),and Accutase. In addition, the cell dissociation agent may be a liquidcomposition in which these components are dissolved or dispersed.

In addition, a working section 40E is disposed in the center on the sideopposite to the carrying-in/carrying-out area 11, namely, at a side wallin the center of the depth side as viewed from thecarrying-in/carrying-out area 11, on the base 10A.

The working section 40E has its working area 41E individuallyoverlapping with a working area 41B of a working section 40B and aworking area 41D of a working section 40D. By this, things for use inprocessing can be moved between the working section 40E and the workingsections 40A and 40B. Therefore, things for use in processing can beaccepted from the carrying-in/carrying-out area 11 through the workingsections 40A and 40B or through the working sections 40C and 40D. Inaddition, things received from the working section 40B or 40D can betransferred to the working section 40D or 40B.

In addition, the working sections 40B and 40E have their working areas41B and 41E overlapping with the processing area 12E, so that operationsin the processing area 12E can be performed there. Therefore, in such acell processing system 1A, operations in the processing area 12D can beperformed from the carrying-in/carrying-out area 11 or by use of theworking section 40A, whereas operations in the processing area 12E canbe performed by use of the working section 40B or the working section40E.

Now, a cell processing method in the present embodiment conducted usingthe aforementioned cell processing system 1A will be described below.Note that when the method in the present embodiment is compared to themethod in the first embodiment, processing in the processing area 12A isreplaced by processing in the processing areas 12D and 12E. Therefore,the following description will be focused on this point, anddescriptions of similar items as above will be omitted.

As aforementioned, the cell processing system 1A has the processingareas 12D and 12E in place of the processing area 12A; therefore, inplace of the operation in the processing area 12A in step S-2 in theabove-described first embodiment, instruments and materials fordispensing a buffer and a cell dissociation agent are disposed andprepared in the processing areas 12D and 12E. In addition, similarly, inplace of the operation in the processing area 12A in steps S-9 and S-10in the above-described first embodiment, the buffer and the celldissociation agent are added, if necessary, in the processing areas 12Dand 12E. In addition, in place of the operation in the processing area12A in step S-13 in the above-described first embodiment, instrumentsand materials for dispensing the buffer and the cell dissociation agentare detached and removed in the processing areas 12D and 12E.

In addition, an automatic operation by the cell processing system 1A iscarried out according to the following procedure.

First, by operations similar to those in steps A-1 to A-7 in the firstembodiment, the cap of the container 100 is detached.

Next, by operations similar to those in steps A-8 to A-11 in the firstembodiment, the culture medium L present in the container main body 110is transported into the collection container 125.

Subsequently, in the processing area 12D, the buffer is dispensed intothe container main body 110. In accordance with an exemplary embodiment,this operation can be carried out similar to that in steps A-12 and A-13in the first embodiment.

Next, using the dispensed buffer, a cell culture 114 present in thecontainer main body 110 is rinsed. This operation can be carried outusing the gripping tool 26, specifically by rotating the container mainbody 110 such that a main surface 113 of the container main body 110 islocated on the lower side, and thereafter vibrating (reciprocating) thecontainer main body 110 horizontally.

Subsequently, by operations similar to those in steps A-8 to A-11 in thefirst embodiment, the buffer (the rinse liquid after the rinsing)present in the container main body 110 is transported into thecollection container 125.

Next, in the processing area 12E, the cell dissociation agent isdispensed into the container main body 110. This operation can becarried out in similar to that in steps A-12 and A-13 in the firstembodiment.

Subsequently, by operations similar to those in steps A-14 and A-15 inthe first embodiment, the container 100 is disposed on the cassette 200.

The above operations are repeated to finish processing for all thecontainers 100, after which the cap is attached to the finally processedcontainer main body 110 by operations similar to those in steps A-16 toA-19.

The other operations can be performed similar to those in theaforementioned method of the first embodiment.

In addition, each of the containers 100 having undergone the aforesaidprocessing can be put to a cell dissociation reaction by the operator.

By the cell processing system and method according to the presentembodiment as above, also, effects similar to those of the firstembodiment can be obtained.

A third embodiment of the present disclosure will be described below.

FIG. 16 is a sectional view of a cell processing system according to athird embodiment of the present disclosure, and FIG. 17 is a schematicview showing an example of a cassette for containers for use in the cellprocessing system shown in FIG. 16. Note that in the figures the sameconfigurations as those in the cell processing system 1 are denoted bythe same reference symbols as used above.

Hereinafter differences of the present embodiment from the firstembodiment will be described in detail below, and descriptions ofsimilar items as above will be omitted.

A cell processing system 1B according to the present embodimentillustrated in FIG. 16 differs from the cell processing system 1 of thefirst embodiment mainly in that it is a system for inoculating cells inthe container 100.

A base 10B in the present embodiment has a configuration wherein aprocessing area 12F for inoculation of cells is disposed in place of andat similar position to the processing area 12A which is a culture mediumdispensing area, a processing area 12G for attachment and detachment ofa cap is disposed at similar position to the processing area 12C, aprocessing area 12H as a depository of the container 100 is disposed inthe carrying-in/carrying-out area 11, and, on the other hand, theprocessing area 12B as a culture medium collection area is omitted.

In the processing area 12F, there are disposed a dispensing pump 121C, astorage container 122C, a tube 123C, and a liquid measurement sensor124C. The dispensing pump 121C, the storage container 122C, the tube123C, and the liquid measurement sensor 124C have configuration similarto that of the dispensing pump 121, the culture medium storage container122, the tube 123, and the liquid measurement sensor 124 except fordifferences in the liquid to be used.

The liquid to be dispensed in the processing area 12F is notparticularly limited so as long it includes cells, and may be, forexample, a dispersion including the above-mentioned cells dispersed in aliquid such as a culture medium or a buffer.

In addition, in the processing area 12G, there is provided a securingbase 129 in addition to the cap depository 128. The securing base 129 isa base for securing the container main body 110, and is provided with asecuring hole 1291 which is a recessed part corresponding to a bottomsurface of the container main body 110. A configuration is adoptedwherein when the container main body 110 is disposed in the securinghole 1291, the opening 111 of the container main body 110 is orientedvertically upward, and at the time of rotating the cap 120 by thegripping tool 26, the securing hole 1291 secures the container main body110 to the securing base 129 such as to prevent the container main body110 from rotating.

In the processing area 12H, a securing pin 127A is disposed. Thesecuring pin 127A is configured to be rotatable, and can be engaged witha cassette 200A. The securing pin 127A can be rotated together with thecassette 200A in accordance with an operation of the robot 20, by adriving mechanism disposed in the base 10B.

As shown in FIG. 17, the cassette 200A is circular disc-like in shape,and is provided on the backside in the center with a hole, which can beengaged with the securing pin 127A. In addition, the cassette 200A isformed with a plurality of recessed parts 201A arranged radially. Therecessed parts 201A are each shaped correspondingly to the bottomsurface of the container 100, and are configured such that the containermain bodies 110 are disposed with their long axes arranged radially inrelation to the cassette 200A in plan view.

By such configurations of the processing area 12H and the cassette 200A,the container 100 for use in processing can be appropriately moved to aplace near the robot 20. Therefore, operations of the robot 20 can besimplified, and the processing is enhanced in efficiency.

Now, a cell processing method of the present embodiment conducted usingthe aforementioned cell processing system 1B will be described below.Note that the following description is focused on differences betweenthe method of the present embodiment and the method of the firstembodiment, and descriptions of similar items as above will be omitted.

First, by operations similar to those in the aforementioned firstembodiment, instruments and materials necessary for inoculation of cellsare disposed and prepared in the processing areas 12F and 12H.

In addition, an automatic operation by the cell processing system 1B iscarried out according to the following procedure.

First, the cap of the container 100 is detached. In regard of this,first, the container 100 is gripped from a lateral side of the containermain body 110 disposed on the cassette 200, by second gripping section262 of the gripping tool 26.

Next, the gripped container 100 is disposed in the securing hole 1291 ofthe securing base 129 in the processing area 12G.

Subsequently, similarly in steps A-1 to A-7 described above, the cap 120of the container 100 disposed on the securing base 129 is detached, andis disposed in a predetermined place.

Next, similarly in steps A-8 and A-9, the container main body 110 isgripped, and the container main body 110 is transported to theprocessing area 12F for inoculation of cells.

Subsequently, the dispensing pump 121C is operated, to dispense apredetermined amount of a cell-containing liquid into the container mainbody 110 through the tube 123C.

Thereafter, similarly in steps A-14 and A-15, the container main body110 is disposed in the recessed part 201A of the cassette 200A.

The above operations are repeated to finish processing for all thecontainers 100, after which, in operations similar to those in stepsA-16 to A-19, the cap is attached to the finally processed containermain body 110.

The other operations can be carried out similar to those in the methodof the first embodiment described above.

By the cell processing system and method according to the presentembodiment as above, also, effects similar to those of the firstembodiment can be obtained.

Note that as a modification of the aforementioned first to thirdembodiments, there can be mentioned, for example, an example wherein asshown in FIG. 18 the same container main body 110 as the container mainbody 110 of other container 100 is used as the cap depository 128A, andthe cap depository disposed on the base is omitted. In such a case, evenin the case where the shape of the container 100 is changed, the capdepository can be easily prepared by utilizing the container 100 of thesame kind. In other words, the cell processing system can be utilized,regardless of the shape of the container 100.

In addition, as another modification, there can be mentioned as thegripping tool, one on which a force sense sensor is mounted. In such acase, since the weight of the container can be sensed, the dispensingamount can be measured by the force sense sensor, even without usingsuch a sensor as a weight sensor as an instrument for dispensing. Inother words, a sensor can be omitted in the processing area fordispensing. In addition, where a force sense sensor is adopted, it isthereby possible, for example, to determine whether or not the grippingtool has made contact with the container. As a result, it is possible,for example, to check whether the gripping tool has made contact withthe container, to dispose the gripping tool in a position suitable forgripping, and to ensure more reliable gripping.

In addition, while the gripping tool has been described as a parallelgripper in each of the aforementioned embodiments, there can be usedvarious grippers such as a rotary gripper, a one-side movable gripper,and a both-side movable gripper.

In addition, the shape of the gripping tool can be changedappropriately.

For instance, in a gripping tool 26A depicted in FIG. 19, in thevicinity of the center of gripping surfaces 266A of first grippingsection 264A, recessed parts 2661 are disposed along an axial direction.The recessed parts 2661 are v-shaped in sectional shape, whereby thearea of contact between the first gripping section 264A and the cap 120is increased when the cap 120 is gripped by the first gripping section264A. Therefore, the cap 120 can be held by the first gripping section264A more securely, and, even in the case of rotating the cap 120 by thefirst gripping section 264A, a rotating force can be transmitted fromthe first gripping section 264A to the cap 120 more reliably.

In addition, for example, the second gripping section of the grippingtool may be provided on only one-side end portions of the first grippingsection.

In addition, in preparing and removing instruments and materials in eachof the processing areas by the operator, the order of operations can bechanged appropriately. Therefore, for example, in respective ones ofsteps S-2 to S-4, steps S-9 to S-12, and steps S-13 to S-15 in the cellprocessing method according to the first embodiment, the order of eachof the steps can be changed.

While the present disclosure has been described above referring to theembodiments illustrated in the drawings, the present disclosure is notlimited to the embodiments.

In the present disclosure, each of the configurations can be replaced byany one that can exhibit an equivalent function, or arbitraryconfigurations may be added.

The detailed description above describes a liquid transport method, acell processing system, and a cell processing method. The invention isnot limited, however, to the precise embodiments and variationsdescribed. Various changes, modifications and equivalents can effectedby one skilled in the art without departing from the spirit and scope ofthe invention as defined in the accompanying claims. It is expresslyintended that all such changes, modifications and equivalents which fallwithin the scope of the claims are embraced by the claims.

What is claimed is:
 1. A liquid transport method in processing of cells,the liquid transport method comprising: a) a step in which lateral sidesof a container holding a liquid is gripped by a gripping tool of a robotfrom a cassette configured to hold a plurality of containers, thecassette having a plurality of recessed parts each shaped correspondingto a bottom surface of the container, the gripping of the containerbeing conducted in such a manner that the gripping tool is not presentover a vertical line of an opening of the container; b) a step in whichthe liquid in the container is transported into a collection containerby rotating the gripped container and orienting the opening of thegripped container toward a vertically lower direction; wherein in stepsa) and b), the robot operates in such a manner as not to pass over avertical line of an opening of the collection container; and wherein thecontainer has a container main body and a cap, the method furthercomprising: detaching the cap of the container from the container mainbody by the robot and disposing the cap on a cap depository prior toconducting the step a); and gripping the lateral sides of the containermain body of the container.
 2. The liquid transport method according toclaim 1, wherein the gripping tool is rotatable, and in step b), thecontainer is rotated, in the same direction, about a center axisconsisting of an axis parallel to an axis of rotation of the grippingtool.
 3. The liquid transport method according to claim 1, wherein instep b), the container is reciprocated up and down when the opening ofthe container is oriented downward.
 4. The liquid transport methodaccording to claim 1, wherein in step b), the rotation of the containeris performed while being accompanied by a translational motion.
 5. Theliquid transport method according to claim 1, wherein the liquid is aculture medium.
 6. A cell processing system, which is a system for usein processing of cells by use of a container, the cell processing systemcomprising: a rectangular base provided with a plurality of processingareas for performing processing by use of the container and acarrying-in/carrying-out area where things for use in the processing canbe carried in and carried out; a robot that is provided on the base andhas a gripping tool capable of gripping at least part of the container,the robot being adjacent to each of the plurality of processing areas; ahousing that covers the processing areas, the robot, and at least partof the carrying-in/carrying-out area and is able to maintain cleanlinessof an inside of the housing; at least one working section that isdisposed on the housing or the base and is configured in such a mannerthat manual operation in the housing from outside of the housing;wherein the gripping tool of the robot can reach each of the processingareas; the housing is configured such that a part of the housingadjacent to the carrying-in/carrying-out area can be opened and closed;the at least one working section is configured such that a workable areaof the at least one working section overlaps with the processing areaand/or the carrying-in/carrying-out area for use in the processing canbe moved between the respective processing areas and thecarrying-in/carrying-out area through the at least one working section;at least one openable and closeable slide shutter, the at least oneopenable and closeable shutter configured to produce a closed systemwhen the at least one shutter is closed; a plurality of suction portionsin the base and in a vicinity of the at least one shutter, the pluralityof suction portions configured to generate a clean space having areduced-pressure state in the clean space; and wherein the plurality ofprocessing areas comprise: a first processing area configured todispense a liquid into the container; a second processing areaconfigured to dispose of and collect a culture medium in the container;and a third processing area configured to attach and detach a cap of thecontainer.
 7. The cell processing system according to claim 6, furthercomprising: a plurality of the working sections, wherein workable areasof the working sections adjacent to each other overlap with each other.8. The cell processing system according to claim 6, wherein manualpreparation for the processing in the processing area can be performedby the working section.
 9. The cell processing system according to claim6, wherein the processing is performed by the robot.
 10. The cellprocessing system according to claim 6, wherein the working section is aglove.
 11. The cell processing system according to claim 6, wherein theliquid is a culture medium.
 12. The cell processing system according toclaim 6, wherein the first processing area includes a dispensing pump, aculture medium storage container for storing a culture medium, a tubefor supplying the culture medium from the culture medium storagecontainer into the container by the dispensing pump, and a liquidmeasurement sensor for measuring the amount of the liquid dispensed intothe container.
 13. The cell processing system according to claim 6,wherein the second processing area includes a collection containerconfigured to collect the culture medium transported from the containerand a sensor configured to measure an amount of the collected culturemedium.
 14. The cell processing system according to claim 13, whereinthe sensor is a weight sensor disposed under the collection container oran optical sensor configured to optically detect an amount of liquid.15. The cell processing system according to claim 14, wherein the thirdprocessing area includes a securing means for securing a cassette forthe container, the container being one of a plurality of containers anda cap depository for supporting the cap detached from the container. 16.A cell processing system, which is a system for use in processing ofcells by use of a container, the cell processing system comprising: arectangular base provided with a plurality of processing areas forperforming processing by use of the container and acarrying-in/carrying-out area where things for use in the processing canbe carried in and carried out, the plurality of processing areasincluding a first processing area configured to dispense a liquid intothe container, a second processing area configured to dispose of andcollect a culture medium in the container, and a third processing areaconfigured to attach and detach a cap of the container; a robot that isprovided on the base and has a gripping tool capable of gripping atleast part of the container, the robot being adjacent to each of theplurality of processing areas; a housing that covers the processingareas, the robot, and at least part of the carrying-in/carrying-out areaand is able to maintain cleanliness of an inside of the housing; aplurality of working sections disposed on the housing or the base andconfigured in such a manner that manual operation in the housing fromoutside of the housing can be performed; wherein the gripping tool ofthe robot can reach each of the processing areas; the housing isconfigured such that a part of the housing adjacent to thecarrying-in/carrying-out area can be opened and closed; and theplurality of working sections include at least two working sections onone side of the rectangular base and at least two working sections on anopposite side of the rectangular base, the plurality of working sectionsbeing configured such that a workable area of the plurality of workingsections overlaps with the processing area and/or thecarrying-in/carrying-out area for use in the processing can be movedbetween the respective processing areas and the carrying-in/carrying-outarea through the plurality of working sections.